There’s new data on the complicated genetic basis of depression and happiness

Four years ago, the public radio program “This American Life” broadcast a remarkable show it called “Switched at Birth.” It described two families—two mothers that one day in 1951 gave birth to baby girls within hours of one another in the same hospital. The families were given the wrong babies to take home. For a bunch of different reasons, the mistake went uncorrected until one mother came forward 43 years later with her suspicions, and then genetic testing was done.

It’s not like there weren’t clues along the way, as “This American Life” host Ira Glass explains:

. . . a quick overview of the two families. The Millers are the bespectacled dark-haired ones from the letter. Mrs. Miller’s husband, the Reverend Norbert Miller, was an evangelical preacher devoted to the church. And they were a bookish, serious bunch. This is a house with a lot of rules. And there were a lot of kids, too—seven kids in all.

The McDonalds are the light-haired ones from the letter. And it was a much smaller family, just two kids. And the feeling in their house was very different from the feeling in the Millers’ house. They were easygoing, quick to laugh and joke around.

And here’s the words of one of the mothers, about the daughter she ended up with:

As Martha grew, she did not look nor act like any other children. She was a delight to all of us, so pretty, so photogenic, so full of life. Our other children were very serious. Martha excelled in music, was a great cheerleader at school, very popular, and a blonde. Our other children had dark hair and all needed glasses for nearsightedness. Martha did not need glasses.

In the great debate about nature versus nurture, we accept that whether you’re blonde or brunette, need glasses or don’t, are genetic traits we can’t do much about. And we sort of accept that being easygoing and quick to laugh are genetic traits too, but surely not to the same extent.

But she also writes that “subtle variation in how we see the world—our biases and quirks of mind—can reshape the actual architecture of our brain, pushing us toward a more optimistic or pessimistic take on life. By changing the way our brain responds to challenges and joys, we can change the way we are.”

Elaine Fox is a psychology professor and director of the Affective Neuroscience Laboratory at the University of Essex and is currently a visiting fellow at Oxford University’s Magdalen College, and she’s my guest today by phone.

Elaine, welcome to the podcast.

Elaine Fox: Hi, Steven. Thanks very much for having me on.

Steven Cherry: So it sounds to me like in the great debate between nature and nurture, you come down squarely on the side of both.

Elaine Fox: Absolutely. And I think really the evidence now really supports that, and perhaps one study will illustrate the point quite nicely. It’s quite a famous study that was published a little bit a while ago now in, I think in the journal Science, in 2003. And this is a study which followed quite a large number of people over a 25-year period, so a long-term study.

All of the participants in the study were about three years of age when the study started, and they were followed and interviewed very extensively every year for the following 25 years. Now, the researchers were interested in whether people with the short version of a gene called the serotonin transporter gene would be at high risk of depression. And there were good biological reasons to suspect that. We know that the short version of this gene has particular effects in the brain, so there was good reason to think that people with the shorter version would be at higher risk of depression than those with the longer version of the gene. They got a full medical test. They were interviewed extensively about what was going on in their lives. And then at the end of the 25-year period, the researchers had a look at the results.

And initially when they looked, they found, much to their surprise, that those with the short version of the gene didn’t actually seem to have any higher risk of depression. However, when they then also took into account the kind of life events that people experienced, a very different picture emerged. And what they found was that those people who had the short version of the gene and also had had three or more really negative life events, really adverse life events, their risk of depression was far, far higher. However, these people with the longer version of the same gene who also had three or more very adverse life events, they didn’t have a higher risk of depression.

So these were two important things that come out of that study. First of all, it tells us the gene alone wasn’t enough to predict a high risk of depression. So those with the shorter version of the gene on its own didn’t confer a higher risk. But it also shows us that the environmental events on their own weren’t enough. So in other words, people who had had three or more pretty nasty things happen to them, they weren’t actually at any higher risk of depression unless they also had the short version of the gene.

So really what the study showed was that a particular combination of environmental events and a particular genetic makeup absolutely formed a kind of a toxic combination. And there’s now lots and lots of other studies that confirm that report.

Steven Cherry: Now you’re using functional magnetic resonance imaging, or fMRI, for some of your research. Aristotle considered the virtues to be a sort of continuum. For example, foolhardiness at one end and cowardice at the other, and courage at the sweet spot in the middle. And I think most of us think of optimism and pessimism in the same way. But you write that our sunny brain is rooted in the pleasure centers, while, and here I’m quoting, “The roots of our rainy brain lie deep among the ancient brain structures that alert us to danger and threat, our fear brain.” So it sounds to me like it’s more like a car with two different pedals, one for acceleration and the other for braking.

Elaine Fox: Well, it’s a little bit like that in terms of both systems, actually. So what I’m really talking about is on the one hand we have the rainy brain system, which is the system that kind of underlies a more pessimistic attitude or an anxious kind of personality style. The key thing, I think, is that what I’m arguing is that we have these very ancient systems in our brain. So in terms of the rainy brain, we have the fear system. So we know that deep in our brain we have an amygdala. And in fact, every creature that moves on the planet has an amygdala. It’s a tiny structure that’s basically like the brain’s alarm system. It’s there to alert us to danger.

Now, in ancient times, that was there to alert us to predators. Nowadays most of us aren’t, you know, worried too much about predators, but now there’s lots of other things to worry about. So we need a functioning fear system. Now, what happens over time is that nerves and fibers link up that ancient amygdala, the fear system, with areas in the frontal cortex, so the more recent areas of our brain in evolutionary terms.

And so that circuit, what I call the rainy brain circuit, does work a little bit like an accelerator and a brake. So that while the amygdala might fire and say, “There’s danger here, we’d better run,” the higher areas in the cortex will tend to dampen things down and put on the brake a little bit. So you get this kind of frame that’s a push-and-pull mechanism between the lower brain areas and the higher brain areas.

And exactly the same kind of mechanism works in the sunny brain side of things. So, again, we have a very ancient system called the nucleus accumbens, which is the pleasure system. Again, it’s an old system in the brain which basically pulls us toward the things that are good for us. So things like warmth, food, shelter, sex, all of those things that are good for either us as individuals or for our species, and the nucleus accumbens tends to underlie all of that. And just as in the rainy brain system, the nucleus accumbens links up to areas in the prefrontal cortex. And, again, it’s very much like a push-and-pull mechanism.

Steven Cherry: So it’s actually more complicated than I made it out, because there’s two cars, each with a brake and accelerator.

Elaine Fox: Exactly. That’s right. It’s like two cars. Exactly.

Steven Cherry: So you think that people can be trained to be more optimistic, or the reverse, I guess. Tell us about Leonardo DiCaprio’s experience.

Elaine Fox: Well, it’s very interesting. So he was—obviously he’s a very, very famous actor. And he was asked to play the role of Howard Hughes in a movie called The Aviator. Now, Howard Hughes had a condition called obsessive compulsive disorder, OCD, and which is characterized by very obsessive or very repetitive behaviors. So things like compulsive hand washing or constantly checking to see if you locked the car, that kind of thing.

So DiCaprio is a method actor, which means that method actors tend to really get into the role before they take on a role. So they’ll often live for weeks or months in a particular role or in a particular lifestyle to really try and get into the head of the person they’re acting. So DiCaprio did this, and he actually went and worked with a psychiatrist in the States, a psychiatrist called Jeffrey Schwartz. And what he did was, he first of all learned a lot about OCD but also interacted with a lot of people who suffered from OCD, and interviewed them and talked to them.

And what actually happened was that over time during the filming of this movie, he actually developed OCD symptoms himself. And to such an extent that when the filming was complete, he actually had to have therapy for about two or three months to wean himself off the OCD. So in a sense, you know, by actually getting his head into the mind-set of somebody who did suffer from obsessive compulsive disorder, DiCaprio himself developed OCD. So that’s a nice demonstration of how if we really kind of almost like mimic a particular mental condition, that can actually start changing in our own heads and in our own behaviors. And, you know, we can actually develop these kind of conditions.

Steven Cherry: So what are some of the things that could have made that bookish, serious girl in the “This American Life” story be more easygoing and quick to laugh?

Elaine Fox: Well, it’s obviously very, very difficult to know. I mean, it’s obviously a very kind of complex mix of, as we’re saying, of genes and of environment. And the other kind of thing that comes into the mix in all of this—well, first of all, I suppose I should say, I mean, a lot of my research is about looking at the fundamental biases that underlie a lot of these rainy brain or sunny brain circuits.

Now the kind of biases I’m looking at are biases that are generally outside our awareness. And there’s a real problem there, because if we’re not aware of something, it’s very, very difficult to study them and, you know, to actually do anything about them. But by using particular techniques, using computers, for example, we flash up pairs of images, say a very nasty image and a very positive image, and then we ask people to search for a target. So they may just have to search for, say, a little yellow square or a blue triangle and press an appropriate button. The trick is that when the target appears near the location of, say, a nasty image, we ­­find that people are a little bit faster. So people who are more pessimistic or more prone to anxiety will be just a little bit quicker in detecting that target if it appears near a nasty image. Whereas if the target is appearing more near a positive, a very nice image, we find that more optimistic, upbeat people tend to zone in there.

So we know that these very fundamental biases absolutely carve our experience of our life, if you like. So whatever’s going on around us, it’s how we—it’s what our brain tunes into automatically and how we interpret situations that really makes a difference. So, for example, that girl, for whatever reason, might have interpreted certain situations in particular ways. And I think that’s one of the fascinating things, I think, is that often we find that events happen, and good and bad things happen to all of us, but it really does make a huge difference in terms of how we interpret that event. That can make a really fundamental difference.

And one of the things I’m really trying to bring out in the book is the idea that we’re effectively training our brain, if you’d like. If we start off with a slight tendency to interpret something in a negative way, over time we’re actually training our brain more and more and more to develop that kind of mind-set. So the example I think I used in the book was it’s a little bit like a—if you think of how water runs through sand, gradually if the water keeps running in the same direction, it will carve out a trench in the sand. And the more the water runs in the same direction, the deeper that trench will become and the harder it will become to change.

Steven Cherry: So in other words, these sort of habits of basically optimism or pessimism actually make changes over time in the brain.

Elaine Fox: Absolutely. And that’s exactly what I see. I really do think these are like habits of mind. So just like habits we might have, these are absolutely habits of mind that become very, very difficult to undo. We tend to get into an entrenched way of seeing things. And as I said, this really flows down to the subliminal biases and even to actual brain circuits. So we know that these habits will lead to real changes in the brain.

Steven Cherry: And you think that really most events in life, I guess some are absolutely bad and some are absolutely good, but most events in life can be looked at either optimistically or pessimistically without there being any difference to the event itself.

Elaine Fox: Yes, that’s right. Yeah, I mean, I think it is a very interesting thing. I mean, obviously there are some awful events that happen and some really bad events. And I think one of the issues is, just to kind of step back a little bit, one of the things I really tried to argue in the book is when I’m talking about optimism, I’m not just talking about positive thinking. This is one of the problems, that there’s a whole kind of positive-thinking movement, if you like, or a lot of self-help books really put forward this theory that, you know, all you need to do is think happy thoughts and think positive thoughts and everything will be fine. And that’s absolutely not what I’m saying in this book.

When I studied optimism, what I realized very quickly was that optimism is actually a construct; there’s a lot of different components to optimism, not just positive thinking. So for example, one important thing is positive actions. We know that actually getting out there and doing things is an absolute key element of optimism. That’s related to positive thinking in some ways, but it is actually quite different. And some of these ways that we’re framing things, sometimes that’s more to do with the actions and the other components of optimism than the actual positive thinking in itself.

Another element of optimism is persistence, for example. We know that in general optimists tend to be more persistent than pessimists. And there’s a very nice experiment we do every year, I do in my lab, actually, with students, just as a demonstration with students. And it works every year. It’s a great experiment to do because it always works out really nicely. And what we simply do is we give the students a questionnaire. So we divide them into optimistic and pessimistic based on this questionnaire measure. And then we just give them a series of anagrams, so a jumble of letters where they just have to come up with words.

So we start them off with a couple of fairly easy anagrams where they come up with the appropriate words. But the key thing is that in there we have an impossible anagram. So there’s actually seven letters where actually there’s no word you can make up at all. So the outcome measure is, How long does it take people before they give up? And time and time again, year after year, what we find is that the optimists take twice as long on average as the pessimists before they give up. So that’s a really nice demonstration of this greater persistence that we know is an important element of optimism.

And, again, there’s a very nice example from Thomas Edison, who invented the electrical light bulb. And he talked about [how] he was going through his lab books and he was trying to invent an electrical lamp. And looking through the lab books, he realized he’d gone through hundreds and thousands of different ways to try and develop a lamp. And he famously said, “We haven’t failed. We’ve just discovered 10,000 ways to build work.” So I think that gives us a kind of an insight into the mind of the optimist. It’s very much about this persistence and actions and other things like having a sense of control in your life, for example.

Steven Cherry: So these actions are sort of symptoms and causes, right? So they reflect our sort of underlying optimism or pessimism. But if we act as an optimist would, we’re actually retraining ourselves to be more optimistic.

Elaine Fox: Absolutely. That’s absolutely right, yes. And I think that’s, when we get back to the reframing, I think that’s one of the things that can really kind of make a difference. And just as an example, if you imagine you walk down the street and you pass by somebody, you notice somebody you haven’t seen for a long time, so an old friend you haven’t seen for a long time. And you’re getting ready to greet them, and suddenly he walks by and snubs you. Now, people can interpret that in very different ways. You might think, “Well, you know, he didn’t recognize me. He was very preoccupied. He might have been busy.” That’s a very positive take on it. Alternatively, you might think, “Oh, he did notice me. He didn’t want to stop and talk. He doesn’t like me. He wasn’t interested.” That’s a more negative take on things.

And but I do, just to add a caveat, say the research is still very much in the early stages. So while there are some good randomized control trials that have been done, there’s still a lot more work to be done to really see whether we can really shift biases, particularly over the longer term, and whether that will really have a big impact on particularly clinical conditions.

Steven Cherry: Very good. Well, I don’t know that there’s a more important problem in science than figuring out the nature of happiness, so thanks for your research, thanks for writing this book, and thanks for joining us today.

Elaine Fox: Thank you very much.

Steven Cherry: We’ve been speaking with psychology professor Elaine Fox, author of the new book Rainy Brain, Sunny Brain, about retraining the brain away from depression and toward greater happiness.

For IEEE Spectrum’s Techwise Conversations, I’m Steven Cherry.

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This interview was recorded 18 July 2012. Segment producer: Barbara Finkelstein; audio engineer: Francesco Ferorelli Read more “Techwise Conversations” or follow us on Twitter.

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